Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Total protein, alpha1-antitrypsin, alpha2-macroglobulin, amylase, methemalbumin, tryptic amidase activity, radioimmunoassayable elastase 2, and three lysosomal hydrolases were determined in the ascites fluid from patients with acute pancreatitis. In eight patients methemalbumin was detected in ascites and serum, supporting the diagnosis of hemorrhagic pancreatitis. Significant levels (4-45 microgram/ml) of tryptic amidase activity were detected in ascites samples from all patients. Evidence is presented which demonstrates that the tryptic amidase activity is due to alpha2-macroglobulin-bound trypsin. Pancreatic elastase 2, determined with a new sensitive and specific radioimmunoassay, ranged from 400 to 2100 ng/ml in serum and from 650 to 4460 ng/ml in ascites fluid. Substantial amounts of alpha2-macroglobulin-bound trypsin and elastase 2, entering the circulation from the peritoneal cavity, might be responsible for certain serious complications seen in acute pancreatitis. However, with the exception of serum calcium and methemalbumin and the ascites fluid methemalbumin and total protein, none of the biochemical parameters studied showed a distinct correlation with the patient's outcome.
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PMID:Studies on the ascites fluid of acute pancreatitis in man. 62 83

Sialophorin (CD43) is the major surface mucin on many hematopoietic cells. It has been implicated in regulating the survival of T lymphocytes in the circulation, and its functions in vitro as the receptor of a T lymphocyte and monocyte activation pathway. The structure of CD43 was examined by protease treatment of lymphoblastoid cells bearing surface CD43. Trypsin treatment converts CD43 (apparent Mr 115,000) to species of apparent Mr 100,000 called T-100, which remains cell-associated; however, the mechanism of trypsin action was not clarified. Pancreatic elastase and Staphylococcus aureus V8 protease cleave CD43 at discrete extracellular sites. V8 protease generates two fragments, which together account for all properties and mass of the parent molecule. The COOH-terminal fragment V-90 (apparent Mr 90,000) consists of the intracellular and transmembrane regions and part of the extracellular region. The fragment V-30 (apparent Mr 30,000), which is released from the cell, comprises the NH2-terminal approximately 78 amino acids with attached oligosaccharides. V-30 contains the binding sites for the antibodies L2 and L10; the latter is the antibody that activates lymphocytes and monocytes. These findings subdivide the extracellular region of CD43 and indicate that the activation-inducing epitope is located in the most distal portion of the molecule. It is shown that CD43 is insensitive to all but very high concentrations of three proteases. Pretreatment with sialidase enhances sensitivity 13-fold for trypsin, 40-fold for S. aureus V8 protease, and 400-fold for elastase, suggesting that sialic acid influences the survival of surface CD43 molecules when cells are exposed to protease.
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PMID:Proteolytic fragmentation of sialophorin (CD43). Localization of the activation-inducing site and examination of the role of sialic acid. 223 Jan 23

Serum elastase-1, amylase, lipase, and trypsin-like immunoreactivity were measured in a group of 17 consecutive patients with acute pancreatitis. When assayed within 24 h of the onset of symptoms, all enzymes were found to be elevated, thus showing similar sensitivity. Elastase-1 did not improve the diagnostic score of the other enzymes studied. Owing to their much quicker and less expensive determinations, amylase and lipase should be considered the best initial markers of pancreatic injury. However, during the course of pancreatitis, amylase and in a lesser degree lipase returned to normal in more cases than elastase or trypsin; both were still elevated in 90% of the patients 10 days after the onset of the symptoms. Thus, trypsin and/or elastase-1 should be reserved for cases of doubtful or delayed diagnosis. The specificity and the positive predictive value of these enzymes need to be evaluated.
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PMID:Comparison of elastase-1 with amylase, lipase, and trypsin-like immunoreactivity in the diagnosis of acute pancreatitis. 243 92

Pulmonary emphysema is thought to be due to an elastase-antielastase imbalance which leads to the destruction of alveolar walls. It is generally agreed that cigarette smoking is the major cause of acquired emphysema although many smokers fail to develop overt disease. Cigarette smoke inactivates alpha 1-proteinase inhibitor (alpha 1PI) which is believed to be the major antielastase in the lower respiratory tract. There is, however, controversy regarding the activity of alpha 1PI in smokers compared with nonsmokers. We, therefore, investigated the trypsin inhibitory capacity (TIC), the pancreatic elastase inhibitory capacity (PEIC), and the amount of immunoreactive alpha 1PI in serum and bronchoalveolar lavage fluid (BALF) of 24 individuals (15 smokers, 5 former smokers, 4 non-smokers) with clinical signs of emphysema and 32 persons (15 smokers, 6 former smokers, 11 non-smokers) without emphysema. Pancreatic elastase is known to be inhibited only by non-oxidised alpha 1PI whereas trypsin is inhibited by both native and oxidised alpha 1PI. Serum values of TIC/alpha 1PI and PEIC/alpha 1PI did not differ between the groups of subjects with emphysema (TIC/alpha 1PI: 0.71 +/- 0.12; PEIC/alpha 1PI: 0.44 +/- 0.06) and without emphysema (TIC/alpha 1PI: 0.68 +/- 0.13; PEIC/alpha 1PI: 0.41 +/- 0.07). Both serum-inhibitory capacities were found to be smaller than unit (= 1) indicating inactivation of alpha 1PI. BALF values of TIC/alpha 1PI showed a wide variation. TIC/alpha 1PI was greater than unity in 84% of subjects with emphysema (2.06 +/- 1.28) compared to 61% without emphysema (1.14 +/- 1.07) providing evidence for the presence of additional inhibitor(s) in those lavage fluids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Functional activity of the alpha1-proteinase inhibitor in serum and bronchoalveolar lavage fluid in congenital lung emphysema]. 278 86

Studies on the effect of leukocyte elastase on the metabolism of chondrocytes in culture have demonstrated that these cells possess a specific cell surface receptor for leukocyte-derived elastase. Purified elastase from rabbit and human leukocytes is capable of modulating the metabolism of the cell by causing a marked decrease in both proteoglycan and protein biosynthesis. Addition of 125I-labeled elastase to chondrocytes maintained in suspension culture has shown that binding occurs, and that it is saturable and is inhibited by the addition of unlabeled enzyme. We ascertained that the active site of the enzyme was necessary for binding to the chondrocyte, since phenylmethylsulfonyl fluoride-inactivated leukocyte elastase failed to bind. Pancreatic elastase had only a slight affinity for the receptor, whereas trypsin and bovine serum albumin failed to bind to any significant extent. Autoradiographic studies and the use of inhibitors of endocytosis, such as dansyl cadaverine, confirmed that endocytosis of elastase was the secondary event after cell binding.
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PMID:Receptor-mediated binding of leukocyte elastase by chondrocytes. 303 97

Active digestive enzymes are involved in the pathophysiology of acute pancreatitis. Previous studies have mainly focused on the role of trypsin in the autodigestive process. The present study compares the noxious potential of different pancreatic enzymes to damage acinar cells. Acinar cells were isolated from rat pancreas by collagenase digestion. Cell viability was studied by (1) exclusion of trypan blue, (2) release of lactate dehydrogenase, and (3) release of newly synthesized proteins identified with methionine labeled with sulfur 35. Cells were then incubated in oxygenated N-2-hydroxyethylpiperazine-N-'-2-ethanesulfonic acid-Ringer solution containing different concentrations of various active digestive enzymes. Uptake of trypan blue was the most sensitive and reliable test of cell damage when compared with release of lactate dehydrogenase or radiolabeled newly synthesized proteins. All active digestive enzymes studied caused dose-dependent cell damage. The noxious potential, however, was strikingly different for the various enzymes. Pancreatic elastase in nanomolar concentrations caused marked cell damage after 45 to 90 minutes of incubation. Lipase and chymotrypsin caused a similar damage only at micromolar concentrations, whereas even millimolar concentrations of trypsin failed to cause significant damage. The present results confirmed recent work showing that lipase and phospholipase A2 probably cause cell damage through release of free fatty acids and lysolecithin. Although activation of trypsin might be the trigger to start the activation cascade in acute pancreatitis, trypsin itself is markedly less noxious to acinar cells when compared with other digestive enzymes. Elastase by far had the greatest noxious potential of all enzymes evaluated. Studies analyzing therapeutic effects of protease inhibitors should evaluate not only the inhibitory potential against trypsin but also that against other digestive enzymes, particularly elastase.
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PMID:Active pancreatic digestive enzymes show striking differences in their potential to damage isolated rat pancreatic acinar cells. 784 75

We have evaluated the diagnostic value of the fecal elastase test in comparison with the secretin-pancreozymin test in the diagnosis of exocrine pancreatic insufficiency. Pancreatic elastase was measured immunologically. Immunoreactive elastase activity in spot stools from controls ranged from 136 to 4440 microgram/g; 95% of all values were within 175 to 1500 microgram/g. The elastase assay CVs ranged from 3.3% to 6.3% (intraassay) and from 4.1% to 10.2% (interassay). The output of elastase correlated well with those of amylase, lipase, and trypsin, yielding respective correlation coefficients of 0.83, 0.82, and 0.84 in controls and 0.86, 0.91, and 0.91 in patients with impaired pancreatic function. In contrast to fecal chymotrypsin, the test results were unaffected by pancreatic enzyme replacement therapy. These results indicate that fecal immunoreactive elastase may be recommended as a new, noninvasive tubeless test of pancreatic function.
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PMID:Immunoreactive elastase I: clinical evaluation of a new noninvasive test of pancreatic function. 859 14

Computerized tomography and ultrasound are helpful in the diagnosis of acute pancreatitis. The procedures, however, are not always available and so laboratory tests continue to play an important role. Serum amylase measurement is the most widely used test, despite its lack of sensitivity (75-92%) and specificity (20-60%). A cut-off point of 3-6 times the upper reference limit increases the specificity greatly, but at the expense of sensitivity. A method using chloronitrophenyl-maltotrioside as substrate has recently been rejected by the IFCC. A method using ethylidene-protected 4-nitrophenyl-maltoheptaoside and a new alpha-glucosidase has emerged as the method of choice. Amylase isoenzyme determinations have higher specificity than total amylase measurements. Serum lipase methods are more sensitive and specific, but methodological problems persist. Cationic trypsin-1 measurements yield high sensitivity but low specificity. Elastase-1 is claimed to correlate best with the clinical symptoms. Reasons for the widely differing reports on sensitivity and specificity of tests for pancreatitis are discussed.
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PMID:Support of the diagnosis of pancreatitis by enzyme tests--old problems, new techniques. 902 27

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